We approached the cell-specific and developmentally regulated expression of proteins within the nervous system using the neuron specific (NSE) and non-neuronal (NNE) enolase isozymes as a model. Human brain cDNA and genomic DNA libraries were constructed so that the genes for these and other brain specific proteins could be isolated and characterized. Using both antibodies and oligonucleotide probes, cDNAs for both human NSE and NNE have been isolated and sequenced. Employing unique regions of these cDNA clones as probes, the developmentally and cell-specific regulated appearance of mRNA for each of these proteins can be investigated using in-situ hydridization. The human chromosome loci for each of these isozymes will be identified. In addition, the isolation of human genomic clones for each of these proteins should provide information on the regulation of expression of neuron and glial specific proteins during cell differentiation of the human nervous system in normal and disease states. The normal specificity of NSE for neural derived cell lines and the availability of specific DNA probes for NSE should provide a useful approach to the characterization of neural derived normal and tumor cell lineages.